UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Nat Rev Rheumatol. 2010 Oct;6(10):607-11. doi: 10.1038/nrrheum.2010.133. Epub 2010 Aug 10.
NFκB is a family of transcription factors involved in immunity and the normal functioning of many tissues. It has been well studied in osteoclasts, and new data indicate an important role for NFκB in the negative regulation of bone formation. In this article, we discuss how NFκB activation affects osteoblast function and bone formation. In particular, we describe how reduced NFκB activity in osteoblasts results in an increase in bone formation via enhanced c-Jun N-terminal kinase (JNK) activity, which regulates FOSL1 (also known as Fra1) expression. Furthermore, we discuss how estrogen and NFκB crosstalk in osteoblasts acts to oppositely regulate bone formation. Future NFκB-targeting treatments for osteoporosis, rheumatoid arthritis and other inflammatory bone diseases could lead to increased bone formation concurrent with decreased bone resorption.
NFκB 是一组参与免疫和许多组织正常功能的转录因子。它在破骨细胞中得到了很好的研究,新的数据表明 NFκB 在负向调节骨形成中起着重要作用。在本文中,我们讨论了 NFκB 的激活如何影响成骨细胞的功能和骨形成。特别是,我们描述了成骨细胞中 NFκB 活性的降低如何通过增强 c-Jun N 末端激酶 (JNK) 活性导致骨形成增加,从而调节 FOSL1(也称为 Fra1)的表达。此外,我们还讨论了成骨细胞中雌激素和 NFκB 的相互作用如何对骨形成进行相反的调节。针对骨质疏松症、类风湿关节炎和其他炎症性骨疾病的 NFκB 靶向治疗可能会导致骨形成增加,同时骨吸收减少。